Haloperidol reduces the sympathetic and thermogenic activation induced by orexin A M. Monda , A. Viggiano, V. De Luca Department of Experimental Medicine, Section of Human Physiology, Second University of Naples, via Costantinopoli 16, 80138 Naples, Italy Received 5 June 2002; accepted 12 September 2002 Abstract This experiment tested the effect of haloperidol on the sympathetic and thermogenic effects induced by orexin A. The firing rates of the sympathetic nerves to interscapular brown adipose tissue (IBAT), along with IBAT and colonic temperatures and heart rate were monitored in urethane-anesthetized male Sprague  /Dawley rats before and 5 h after an injection of orexin A (1.5 nmol) into the lateral cerebral ventricle. The same variables were monitored in rats with an intraperitoneal administration of haloperidol (1 mg/kg bw), a D 2 receptor antagonist. The results show that orexin A increases the sympathetic firing rate, IBAT and colonic temperatures and heart rate. This increase is reduced by the haloperidol. These findings suggest that dopaminergic system is activated during the orexin A-induced hyperthermia. # 2002 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved. Keywords: Body temperature; Haloperidol; Orexin A; Rat; Sympathetic activity 1. Introduction Orexin A (Sakurai et al., 1998), hypothalamic peptide so-called for its stimulation on food intake (Sweet et al., 1999), causes vegetative responses, when this peptide is intracerebroventricularly (icv) injected (Lubkin and Stricker-Krongrad, 1998; Shirasaka et al., 1999). The autonomic reactions include the sympathetic and ther- mogenic changes. Indeed, an icv administration of orexin A induces an increase in firing rate of the sympathetic nerves to interscapular brown adipose tissue (IBAT), accompanied with a rise in IBAT and colonic temperatures (Monda et al., 2001). A role of orexins in sleep regulation has been demonstrated (Beuckmann and Yanagisawa, 2002). Deficiency in orexin neurotransmission results in the sleep disorder narcolepsy in mice, dogs, and humans (Taheri et al., 2002). Intraperitonel administration of haloperidol produces hypothermic effects in the rats (Lin et al., 1979), and in the rabbits (Vybiral and Vesela, 1994). Oral administra- tion of haloperidol in normal volunteers causes signifi- cant attenuation of the normal daytime increase of body temperature (De Koning and De Vries, 1995). This indicates that dopaminergic system is involved in the regulation of body temperature. Furthermore, an intraperitoneal administration of haloperidol reduces the hyperlocomotion induced by an icv injection of orexin A, suggesting an involvement of dopaminergic system in the motor reactions due to orexin A (Nakamura et al., 2000). The aim of this experiment was to test the effects of haloperidol on the sympathetic and thermogenic reac- tions induced by orexin A, so that a possible involve- ment of the dopaminergic system could be considered. 2. Materials and methods 2.1. Animals Male Sprague  /Dawley rats (n /24), 3 months old and weighing 270 /320 g were used in the experiments. The rats were housed in pairs at controlled temperature (229 /1 8C) and humidity (70%) with a 12:12 h light /  Corresponding author. Tel.:  /39-81-566-5833; fax:  /39-81-566- 5846 E-mail address: marcellino.monda@unina2.it (M. Monda). Neuroscience Research 45 (2003) 17  /23 www.elsevier.com/locate/neures 0168-0102/02/$ - see front matter # 2002 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved. PII:S0168-0102(02)00191-8